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Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid.
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Anti-pituitary-specific transcription factor (PIT)-1 hypophysitis is an autoimmune disease characterized by hormone secretion impairment from PIT-1-expressing pituitary cells, accompanied by malignancies with ectopic PIT-1 expression. Cytotoxic T cells (CTL) targeting PIT-1-positive cells have been implicated in disease development, yet direct evidence is lacking. As human leukocyte antigen (HLA)-matching is required for modeling T cell-mediated autoimmune diseases, we employ induced pluripotent stem cells (iPSC) to generate pituitary organoids harboring the patients' HLA haplotype and coculture the organoids with PIT-1-reactive CTLs isolated from the patients' peripheral blood mononuclear cells.
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Multi-cellular organoids are self-assembly aggregates that mimic biological functions and developmental processes of many tissue types in vitro. They are widely employed for disease modeling and functional studies. Hypothalamus-pituitary organoids can be generated through differentiation induction from pluripotent stem cells.
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